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LATS2 expression differences in lung adenocarcinoma and lung squamous cell carcinoma analyzed using bioinformatics and experimental approaches

  • Authors:
    • Zhen Zhang
    • Shaoyan Zhang
    • Yalai Xu
    • Changyu Zhang
    • Xudong Zhang
  • View Affiliations / Copyright

    Affiliations: Department of Oncology Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, P.R. China, School Infirmary, Henan Vocational College of Water Conservancy and Environment, Zhengzhou, Henan 450000, P.R. China, Department of Respiratory Medicine, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, P.R. China
    Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 316
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    Published online on: May 28, 2026
       https://doi.org/10.3892/ol.2026.15671
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Abstract

The present study aimed to investigate the role and expression of large tumor suppressor kinase 2 (LATS2) in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). The expression levels of LATS2 in LUAD and LUSC, as well as their association with clinical characteristics and patient survival, were analyzed using data obtained from The Cancer Genome Atlas. A total of 100 LATS2‑related genes were screened to conduct Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analyses. The association between LATS2 expression and immune cell infiltration, particularly CD4+ and CD8+ tumor‑infiltrating lymphocytes (TILs), was analyzed. The role of LATS2 in tumor cells was validated by observing the changes in proliferation, apoptosis, migration and invasion of LUAD and LUSC cells following LATS2 overexpression. LATS2 expression was low in both LUAD and LUSC. In LUAD, high expression of LATS2 was associated with lymph node metastasis, distant metastasis and TNM stage and served as an independent risk factor for both overall survival and progression‑free survival. Conversely, in LUSC, LATS2 exhibited a weak association with clinical characteristics and survival. In LUAD and LUSC, LATS2‑related genes exhibited differences in their associated functional pathways and biological processes. In LUAD, LATS2 was positively associated with CD4+ TIL proportions and CD4+/CD8+ TIL proportions, while exhibiting a negative association with CD8+ TIL proportions. In LUSC, no such associations were observed. In vitro experiments demonstrated that overexpression of LATS2 inhibited proliferation, migration and invasion, while promoting apoptosis, in both LUAD and LUSC cell lines, with notably stronger effects observed in LUAD cells. In conclusion, LATS2 exerts tumor‑suppressive functions in both LUAD and LUSC. In LUAD, LATS2 is an independent risk factor for patient survival, possibly due to its close association with CD8+ TIL levels; however, this relationship is not pronounced in LUSC.
View Figures

Figure 1

Comprehensive expression analysis of
LATS2 in LUAD and LUSC. (A) Expression levels of LATS2 in LUAD and
LUSC analyzed using the Gene Set Cancer Analysis platform. (B)
Comparative analysis of LATS2 expression between tumor and normal
tissues in LUAD using independent sample t-test and paired sample
t-test. (C) Comparative analysis of LATS2 expression between tumor
and normal tissues in LUSC using independent sample t-test and
paired sample t-test. (D) Differential expression of LATS2 between
LUAD and LUSC tumor tissues. (E) Immunohistochemical validation of
LATS2 expression in LUAD, LUSC and normal lung tissues using the
Human Protein Atlas database (antibody ID: 039191). All the data
are presented as mean ± SD. ***P<0.001. LATS2, large tumor
suppressor kinase 2; LUAD, lung adenocarcinoma; LUSC, lung squamous
cell carcinoma; TPM, transcripts per million; RSEM, RNA-seq by
expectation-maximization.

Figure 2

Correlation between LATS2 expression
and clinical characteristics in LUAD and LUSC. (A) Stratified
analysis of LATS2 expression across T, N and M stage and TNM stage
in LUAD. (B) Stratified analysis of LATS2 expression across T
stage, N stage, M stage and TNM stage in LUSC. All the data are
presented as mean ± SD. *P<0.05. LATS2, large tumor suppressor
kinase 2; LUAD, lung adenocarcinoma; LUSC, lung squamous cell
carcinoma; T, tumor size; N, lymph node metastasis; M, distant
metastasis; TPM, transcripts per million.

Figure 3

Prognostic significance of LATS2
expression in LUAD and LUSC survival analyses. Kaplan-Meier curves
demonstrating association between LATS2 expression and (A) OS or
(B) PFS in LUAD using log-rank test. Forest plots illustrating
hazard ratios for (C) OS or (D) PFS in LUAD patients with LUAD. (E)
Kaplan-Meier survival curves of LATS2 for OS in patients LUSC using
the two-stage method. (F) Kaplan-Meier survival curves of LATS2 for
OS or PFS in patients with LUSC, using the log-rank test. Forest
plots illustrating hazard ratios for (G) OS or (H) PFS in patients
with LUSC. OS, overall survival; PFA, progression-free survival;
LATS2, large tumor suppressor kinase 2; LUAD, lung adenocarcinoma;
LUSC, lung squamous cell carcinoma; T stage; tumor size; N, lymph
node metastasis.

Figure 4

KEGG and GO analysis of
LATS2-correlated genes. (A) Workflow for identifying
LATS2-correlated genes prior to GO and KEGG enrichment analysis.
(B) GO enrichment analysis revealing biological processes, cellular
components and molecular functions associated with LATS2-associated
genes in LUAD/LUSC. (C) KEGG pathway analysis identifying signaling
pathways enriched in LATS2-correlated genes across LUAD/LUSC.
LATS2, large tumor suppressor kinase 2; LUAD, lung adenocarcinoma;
LUSC, lung squamous cell carcinoma; KEGG, Kyoto Encyclopedia of
Genes and Genomes; GO, Gene Ontology; BP, biological
process; CC, cellular component; MF, molecular function; ECM,
extracellular matrix.

Figure 5

Immune infiltration landscape
associated with LATS2 expression. (A and B) Differential immune
cell infiltration profiles between LATS2 high/low expression groups
using CIBERSORT algorithm in LUAD/LUSC. Correlation between LATS2
mRNA expression and (C) CD4+ or (D) CD8+ T
cell infiltration in LUAD via the GSCA database. Correlation
between LATS2 mRNA expression and (E) CD4+ T or (F)
CD+ T cell infiltration in LUSC via the GSCA database.
NK, natural killer; LATS2, large tumor suppressor kinase 2; LUAD,
lung adenocarcinoma; LUSC, lung squamous cell carcinoma; GSCA, Gene
Set Cancer Analysis; FDR, false discovery rate; ImmuCellAI, immune
cell abundance identifier.

Figure 6

Correlation between the expression of
LATS2 and the distribution of CD4+ and CD8+
TILs in LUAD/LUSC tissues. Distributions of CD4+ and
CD8+ TILs in (A) LUAD or (B) LUSC tissues. (C)
Comparative analysis of CD4+/CD8+ TIL
proportion and LATS2 expression levels between LUAD and LUSC
cohorts. (D) Multivariate correlation analysis of LATS2 expression
with CD4+ TIL proportion, CD8+ TIL proportion
and CD4+/CD8+ ratio in LUAD/LUSC. All data
are presented as mean ± SD, all comparisons were conducted using
independent samples t-test. *P<0.05. LATS2, large tumor
suppressor kinase 2; LUAD, lung adenocarcinoma; LUSC, lung squamous
cell carcinoma; TILs, tumor-infiltrating lymphocytes.

Figure 7

Functional impact of LATS2
upregulation on LUAD/LUSC cell viability and apoptosis. (A)
Baseline LATS2 expression comparison in A549 (LUAD), SK-MES-1
(LUSC) and Beas-2B (normal bronchial) cell lines. (B) Western blot
validation of LATS2 protein overexpression post-transfection. (C)
Transfection efficiency confirmation via fluorescence labeling
(MOI=10; transfection rate=90.5 and 90% in LUAD and LUSC,
respectively). Scale bar, 100 µm. (D) qPCR quantification of LATS2
mRNA induction post-transfection. (E) MTT assay evaluation of cell
proliferation changes following LATS2 upregulation. (F) Flow
cytometry analysis of apoptosis rate alterations after LATS2
upregulation. Data are presented as mean ± SD and all comparisons
were conducted using independent samples t-test. *P<0.05,
**P<0.01 and ***P<0.001. LATS2, large tumor suppressor kinase
2; LUAD, lung adenocarcinoma; LUSC, lung squamous cell carcinoma;
BC, blank control; NC, negative control; OE, overexpression; OD,
optical density; MOI, multiplicity of infection; qPCR, quantitative
PCR.

Figure 8

Influence of LATS2 overexpression on
LUAD and LUSC cell migration and invasion. (A) Wound healing assay
in A549 cells. (B) Wound healing assay in SK-MES-1 cell lines. (C)
Transwell assay evaluating altered invasive capacity of A549 and
SK-MES-1 cells. (D) Comparison of cell migration rates. (E)
Comparison of number of invading cells. Scale bar, 100 µm,
**P<0.01 and ***P<0.001. LUAD, lung adenocarcinoma; LUSC,
lung squamous cell carcinoma; LATS2, large tumor suppressor kinase
2; BC, blank control; NC, negative control; OE, overexpression.
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Copy and paste a formatted citation
Spandidos Publications style
Zhang Z, Zhang S, Xu Y, Zhang C and Zhang X: LATS2 expression differences in lung adenocarcinoma and lung squamous cell carcinoma analyzed using bioinformatics and experimental approaches. Oncol Lett 32: 316, 2026.
APA
Zhang, Z., Zhang, S., Xu, Y., Zhang, C., & Zhang, X. (2026). LATS2 expression differences in lung adenocarcinoma and lung squamous cell carcinoma analyzed using bioinformatics and experimental approaches. Oncology Letters, 32, 316. https://doi.org/10.3892/ol.2026.15671
MLA
Zhang, Z., Zhang, S., Xu, Y., Zhang, C., Zhang, X."LATS2 expression differences in lung adenocarcinoma and lung squamous cell carcinoma analyzed using bioinformatics and experimental approaches". Oncology Letters 32.1 (2026): 316.
Chicago
Zhang, Z., Zhang, S., Xu, Y., Zhang, C., Zhang, X."LATS2 expression differences in lung adenocarcinoma and lung squamous cell carcinoma analyzed using bioinformatics and experimental approaches". Oncology Letters 32, no. 1 (2026): 316. https://doi.org/10.3892/ol.2026.15671
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Spandidos Publications style
Zhang Z, Zhang S, Xu Y, Zhang C and Zhang X: LATS2 expression differences in lung adenocarcinoma and lung squamous cell carcinoma analyzed using bioinformatics and experimental approaches. Oncol Lett 32: 316, 2026.
APA
Zhang, Z., Zhang, S., Xu, Y., Zhang, C., & Zhang, X. (2026). LATS2 expression differences in lung adenocarcinoma and lung squamous cell carcinoma analyzed using bioinformatics and experimental approaches. Oncology Letters, 32, 316. https://doi.org/10.3892/ol.2026.15671
MLA
Zhang, Z., Zhang, S., Xu, Y., Zhang, C., Zhang, X."LATS2 expression differences in lung adenocarcinoma and lung squamous cell carcinoma analyzed using bioinformatics and experimental approaches". Oncology Letters 32.1 (2026): 316.
Chicago
Zhang, Z., Zhang, S., Xu, Y., Zhang, C., Zhang, X."LATS2 expression differences in lung adenocarcinoma and lung squamous cell carcinoma analyzed using bioinformatics and experimental approaches". Oncology Letters 32, no. 1 (2026): 316. https://doi.org/10.3892/ol.2026.15671
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